Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism

This study is currently recruiting participants.
Verified March 2013 by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor:
Information provided by (Responsible Party):
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier:
NCT01824121
First received: March 31, 2013
Last updated: NA
Last verified: March 2013
History: No changes posted
  Purpose

There is evidence suggesting that stem cells harvested from the bone marrow and transplanted into the brain may be effective in slowing down the progression of parkinsonism. Mesenchymal stem cells are able to produce growth factors that provide support to diseased nervous cells.

In this study mesenchymal stem cells will be harvested from the bone marrow, cultivated in a test tube so that they multiply and then infused into the arteries that supply blood to the brain in 20 patients suffering from a rare form of parkinsonism, Progressive Supranuclear Palsy. Each patient will undergo two infusions, one with the stem cells and one without, at an interval of 6 months. The sequence of the two infusions will be assigned randomly; patients and assessors will not know the sequence (double-blind). Patients will be followed-up for up to 1 year after the last infusion, with regular assessments to assess safety, efficacy on motor and cognitive functions, and effects on the brain by neuroimaging techniques.

The study has a preliminary phase with 5 patients all given stem cell therapy alone, designed to assess safety


Condition Intervention Phase
Progressive Supranuclear Palsy
Biological: stem cell therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Autologous Mesenchymal Stem Cell Therapy in Progressive Supranuclear Palsy: a Randomized, Double-blind, Controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:

Primary Outcome Measures:
  • incidence of adverse events [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    incidence of adverse events collected by clinical monitoring and performing routine laboratory tests


Secondary Outcome Measures:
  • changes in brain images [ Time Frame: one year ] [ Designated as safety issue: No ]
    change vs baseline in the striatal density of dopamine transporters in SPECT brain images and in the normalized regional cerebral flow / glucose metabolism in the gray matter in PET brain images after one year


Other Outcome Measures:
  • changes in motor function [ Time Frame: one year ] [ Designated as safety issue: No ]
    changes vs baseline in total and motor UPDRS scores, Hoehn & Yahr staging, SEADL score, CGI and multifactorial movement analysis

  • changes in cognitive functions [ Time Frame: one year ] [ Designated as safety issue: No ]
    changes vs baseline in MMSE score and in a series of neuropsychological measures (verbal comprehension, perceptual organization, immediate memory, delayed memory, word list recognition, language attention / concentration, visuospatial ability, processing speed, executive function)


Estimated Enrollment: 25
Study Start Date: December 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: immediate stem cell therapy
patients will undergo active intervention i.e. they will be given stem cell therapy immediately. After 6 months they will undergo a sham procedure.
Biological: stem cell therapy
Bone marrow will be collected from the iliac crest under local anesthesia. Mesenchymal Stem Cells (MSCs) will be isolated and cultivated in vitro. Patients will be catheterized and the MSCs will then be administered by intra-arterial route via the internal carotid artery and the vertebral artery that is largest in caliber, injecting small boluses manually through a microcatheter.
Sham Comparator: delayed stem cell therapy
patients allocated to delayed stem cell therapy will undergo a sham procedure (incannulation of the femoral vein and infusion of saline solution). They will receive stem cell therapy after 6 months
Biological: stem cell therapy
Bone marrow will be collected from the iliac crest under local anesthesia. Mesenchymal Stem Cells (MSCs) will be isolated and cultivated in vitro. Patients will be catheterized and the MSCs will then be administered by intra-arterial route via the internal carotid artery and the vertebral artery that is largest in caliber, injecting small boluses manually through a microcatheter.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

diagnosis of 'probable Progressive Supranuclear Palsy - Richardson's disease subtype' according to current diagnostic criteria (Litvan et al. 1996 and 2003)

  • age at onset at least 40 years;
  • disease duration 12 months to 8 years;
  • supranuclear ophthalmoplegia;
  • postural instability or falls within 3 years from disease onset
  • positive MRI for PSP criteria (Quattrone et al, 2008)
  • Stable pharmacological treatment for at least 90 days
  • Lack of response to chronic levodopa (at least 12-month treatment).
  • Able to stand in upright posture without assistance for at least 30 seconds
  • Written informed consent (including video taping)

Exclusion Criteria:

  • Idiopathic Parkinson's disease;
  • Cerebellar ataxia
  • Symptomatic autonomic dysfunction
  • Evidence of any other neurological disease that could explain signs;
  • History of repeated strokes with stepwise progression of parkinsonian features;
  • History of major stroke;
  • Any history of severe or repeated head injury;
  • A history of encephalitis;
  • A history of neuroleptic use for a prolonged period of time or within the past 6 months;
  • Street-drug related parkinsonism;
  • Significant other neurological disease on CT-scan/MRI;
  • Oculogyric crises;
  • Major signs of corticobasal degeneration;
  • Signs of Lewy body disease;
  • Other life-threatening disease likely to interfere with the main outcome measure;
  • Any clinically significant laboratory abnormality, with the exception of cholesterol, triglycerides and glucose;
  • Renal failure (serum creatinine more than 300 mM/l);
  • Transaminase elevation more than twice the upper limit of normal;
  • Any concomitant disorder associated with bone marrow function impairment
  • Any concomitant disorder that requires chronic treatment with immunosuppressors, anti-inflammatory agents, and/or growth factors
  • dementia (MMSE < 24 according to Folstein 1975 or defined according to DSM-IV TR criteria)
  • any other disorder that could interfere with the evaluation of treatment or that could make intra-arterial infusion inadvisable
  • any other features that, according to the investigator, could reduce adherence to protocol procedures or prevent rapid access in case of emergency;
  • women of child-bearing age
  • participation in another clinical trial with experimental treatment in the last 30 days
  • brain MRI evidence of severe vascular abnormalities, space-occupying lesions or normal pressure hydrocephalus
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01824121

Contacts
Contact: Margherita Canesi, MD 0039 02 5799 ext 3353 canesi@parkinson.it

Locations
Italy
ICP Parkinson Institute Recruiting
Milano, Italy, 20126
Principal Investigator: Gianni Pezzoli, MD         
Sub-Investigator: Margherita Canesi, MD         
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Investigators
Principal Investigator: Rosaria Giordano, MD IRCCS Ca' Granda Ospedale Maggiore Policlinico
  More Information

No publications provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier: NCT01824121     History of Changes
Other Study ID Numbers: 032011, 2011-004051-39
Study First Received: March 31, 2013
Last Updated: March 31, 2013
Health Authority: Italy: Ministry of Health

Keywords provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Progressive Supranuclear palsy
stem cell therapy

Additional relevant MeSH terms:
Supranuclear Palsy, Progressive
Paralysis
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Tauopathies
Neurodegenerative Diseases
Neurologic Manifestations
Eye Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on April 17, 2014